The Role of Serum High Density Lipoproteins in Adrenal Steroidogenesis

Gwynne, John T.; Hess, Barbara; Hughes, Thomas A.; Rountree, Robert; Mahaffee, D D

doi:10.1080/07435808409036509

Cited by 33 publications

(24 citation statements)

References 35 publications

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“…In addition, expression of the LDL receptor (LDLR) has also been detected on glucocorticoid-producing cells of the adrenal zona fasciculata (Fong et al 1989). In line with this, in vitro studies have suggested that both HDL and LDL fractions are capable of supplying cholesterol to the steroidogenic pool of cultured adrenocortical cells (Gwynne & Hess 1980, Higashijima et al 1987, Rainey et al 1992, Yaguchi et al 1998.…”

Section: Introductionmentioning

confidence: 76%

Adrenocortical LDL receptor function negatively influences glucocorticoid output

Sluis

Eck

Hoekstra

2015

Journal of Endocrinology

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Over 50% of the cholesterol needed by adrenocortical cells for the production of glucocorticoids is derived from lipoproteins. However, the overall contribution of the different lipoproteins and associated uptake pathways to steroidogenesis remains to be determined. Here we aimed to show the importance of LDL receptor (LDLR)-mediated cholesterol acquisition for adrenal steroidogenesis in vivo. Female total body LDLR knockout mice with a human-like lipoprotein profile were bilaterally adrenalectomized and subsequently provided with one adrenal either expressing or genetically lacking the LDLR under their renal capsule to solely modulate adrenocortical LDLR function. Plasma total cholesterol levels and basal plasma corticosterone levels were identical in the two types of adrenal transplanted mice. Strikingly, restoration of adrenal LDLR function significantly reduced the ACTH-mediated stimulation of adrenal steroidogenesis (P!0.001), with plasma corticosterone levels that were respectively 44-59% lower (P!0.01) as compared to adrenal LDLR negative controls. In addition, LDLR positive adrenal transplanted mice exhibited a significant decrease (K39%; P!0.001) in their plasma corticosterone level under fasting stress conditions. Biochemical analysis did not show changes in the expression of genes involved in cholesterol mobilization. However, LDLR expressing adrenal transplants displayed a marked 62% reduction (P!0.05) in the transcript level of the key steroidogenic enzyme HSD3B2. In conclusion, our studies in a mouse model with a human-like lipoprotein profile provide the first in vivo evidence for a novel inhibitory role of the LDLR in the control of adrenal glucocorticoid production.

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Section: Introductionmentioning

confidence: 76%

Adrenocortical LDL receptor function negatively influences glucocorticoid output

Sluis

Eck

Hoekstra

2015

Journal of Endocrinology

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“…The influence of lipoproteins on steroidogenesis has also been investigated by previous workers, although the majority of studies have been performed from a non-endocrinological perspective with the primary interest being directed towards the biochemistry of cholesterol per se and its subsequent uptake and metabolism, rather than the modulation of glucocorticoid secretion and synthesis. These studies on lipoprotein metabolism have revealed that LDL-cholesterol is preferentially utilised in mice (Faust et al 1977) and human fetal cells , Carr et al 1980, Higashijima et al 1987, whilst HDL-cholesterol is the preferred substrate in rats (Gwynne et al 1976, Andersen & Dietschy 1978, Gwynne & Hess 1980. Studies using bovine adrenocortical cells have demonstrated variable results and few have directly compared the relative effects of HDL and LDL, although preincubation with either lipoprotein increased both basal and ACTH-stimulated steroidogenesis (Koper et al 1985).…”

Section: Discussionmentioning

confidence: 99%

The influence of plasma on basal and ACTH-stimulated in vitro adrenocortical steroidogenesis

Jenkins¹,

Cross²,

Perry³

et al. 1999

Journal of Endocrinology

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Early descriptions of in vitro ACTH bioassays all emphasised the need to use extracted plasma samples due to interference by an unidentified component. The aim of these studies was to elucidate the effects of whole plasma on ACTH steroidogenic activity in vitro and to identify the responsible factor. A sensitive in vitro dispersed bovine adrenocortical cell bioassay was established. The addition of 10% ACTH-depleted human pooled plasma to the incubation media resulted in basal steroidogenesis equivalent to that achieved with 10 9 M ACTH 1-24 and potentiated the steroidogenic activity of 10 9 M ACTH 1-24 by 7·8-fold. This potentiation was dependent on the concentration of both ACTH and plasma in the media, but did not result from the mitogenic effect of plasma. A pituitary source was excluded and the potentiating activity was not extractable by Vycor glass. Column chromatography demonstrated two peaks of activity corresponding to molecular weights of 650 and 220 10 3 Da. These peaks did not correspond to the plasma binding of 125 I-ACTH which resulted from non-specific binding to albumin. Lipoprotein-deficient serum had no effect on either basal or ACTH-stimulated steroidogenesis, but both were restored by the addition of purified lipoproteins. However, novel findings demonstrated a differential effect of low (LDL) and high (HDL) density lipoproteins on basal and ACTH-stimulated steroid production; thus, LDL exerted a greater effect on the former, whilst HDL potentiated the steroidogenic activity of added ACTH more than LDL. The addition of the lipoproteins to lipoprotein-deficient serum restored its basal and ACTH potentiating effects, the cholesterol concentrations of the chromatographic fractions exactly paralleling their ACTH potentiating effect. These findings suggest that not only are lipoproteins the plasma factor(s) which potentiates ACTH steroidogenic activity in in vitro bioassays, but also that they exert differential effects on basal and ACTH-stimulated steroid production.

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“…HDL CE selective uptake is defined as the movement of CE from HDL into target cells without significant internalization and degradation of the HDL particle (Gwynne and Hess, 1980;Glass et al, 1983;Stein et al, 1983;Reaven et al, 1984;Glass et al, 1985;Pittman et al, 1987). This mechanism is distinct from that of the LDL receptor pathway, where LDL is internalized and the particle is degraded in the endosomal/lysosomal pathway (Brown and Goldstein, 1986).…”

Section: Introductionmentioning

confidence: 99%

Scavenger Receptor BI (SR-BI) Clustered on Microvillar Extensions Suggests that This Plasma Membrane Domain Is a Way Station for Cholesterol Trafficking between Cells and High-Density Lipoprotein

Peng

Akmentin

Connelly

et al. 2004

MBoC

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Receptor-mediated trafficking of cholesterol between lipoproteins and cells is a fundamental biological process at the organismal and cellular levels. In contrast to the well-studied pathway of LDL receptor-mediated endocytosis, little is known about the trafficking of high-density lipoprotein (HDL) cholesterol by the HDL receptor, scavenger receptor BI (SR-BI). SR-BI mediates HDL cholesteryl ester uptake in a process in which HDL lipids are selectively transferred to the cell membrane without the uptake and degradation of the HDL particle. We report here the cell surface locale where the trafficking of HDL cholesterol occurs. Fluorescence confocal microscopy showed SR-BI in patches and small extensions of the cell surface that were distinct from sites of caveolin-1 expression. Electron microscopy showed SR-BI in patches or clusters primarily on microvillar extensions of the plasma membrane. The organization of SR-BI in this manner suggests that this microvillar domain is a way station for cholesterol trafficking between HDL and cells. The types of phospholipids in this domain are unknown, but SR-BI is not strongly associated with classical membrane rafts rich in detergent-resistant saturated phospholipids. We speculate that SR-BI is in a more fluid membrane domain that will favor rapid cholesterol flux between the membrane and HDL.

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The Role of Serum High Density Lipoproteins in Adrenal Steroidogenesis

Cited by 33 publications

References 35 publications

Adrenocortical LDL receptor function negatively influences glucocorticoid output

Adrenocortical LDL receptor function negatively influences glucocorticoid output

The influence of plasma on basal and ACTH-stimulated in vitro adrenocortical steroidogenesis

Scavenger Receptor BI (SR-BI) Clustered on Microvillar Extensions Suggests that This Plasma Membrane Domain Is a Way Station for Cholesterol Trafficking between Cells and High-Density Lipoprotein

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